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| Content Provider | PubMed Central |
|---|---|
| Author | Murali, Sindhubarathi Zhang, Min Nurse, Colin A. |
| Copyright Year | 2014 |
| Abstract | A local angiotensin-generating system is present in the carotid body (CB) and increased angiotensin II (ANG II) signalling contributes to enhanced CB excitation in chronic heart failure (CHF) and after chronic or intermittent hypoxia. ANG II actions have thus far been attributed solely to stimulation of AT1 receptors (AT1Rs) on chemoreceptor type I cells. Here, we show that in dissociated rat CB cultures, ANG II also stimulates glial-like type II cells, identified by P2Y2-receptor-induced intracellular Ca2+ elevation (Δ[Ca2+]i). ANG II induced a dose-dependent (EC50 ∼8 nm), robust Δ[Ca2+]i in type II cells that was reversibly abolished by the AT1R blocker losartan (1 μm). The ANG II-induced Δ[Ca2+]i persisted in Ca2+-free medium but was sensitive to store depletion with cyclopiazonic acid (1 μm). Similar to P2Y2 receptor agonists, ANG II (20–1000 nm) activated pannexin-1 (Panx-1) current that was reversibly abolished by carbenoxolone (5 μm). This current arose with a variable delay and was reversibly inhibited by losartan. Repeated application of ANG II often led to current run-down, attributable to AT1R desensitization. When applied to the same cell the combined actions of ANG II and ATP on Panx-1 current were synergistic. Current induced by either ligand was inhibited by BAPTA-AM (1 μm), suggesting that intracellular Ca2+ signalling contributed to Panx-1 channel activation. Because open Panx-1 channels release ATP, a key CB excitatory neurotransmitter, it is plausible that paracrine stimulation of type II cells by ANG II contributes to enhanced CB excitability, especially in pathophysiological conditions such as CHF and sleep apnoea. |
| Related Links | http://dx.doi.org/10.1113/jphysiol.2014.279299 |
| Ending Page | 4762 |
| Page Count | 16 |
| Starting Page | 4747 |
| File Format | |
| ISSN | 14697793 |
| e-ISSN | 14697793 |
| Journal | The Journal of Physiology |
| Issue Number | Pt 21 |
| Volume Number | 592 |
| Language | English |
| Publisher | BlackWell Publishing Ltd |
| Publisher Date | 2014-11-01 |
| Access Restriction | Open |
| Rights Holder | BlackWell Publishing Ltd |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
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